In vitro and in vivo modulation of cholinergic muscarinic receptors in rat lymphocytes and brain by cholinergic agents.
A binding site for 3H-quinuclidinyl benzylate (QNB) has been identified in rat lymphocytes which has the characteristics of a cholinergic muscarinic receptor (Costa, L. G., Kaylor, G. & Murphy, S. D. (1988). Muscarinic cholinergic binding sites on rat lymphocytes. Immunopharmacology, 16, 139-149.) Here we show that prolonged exposures to cholinergic compounds in vitro and in vivo modulate muscarinic receptor binding in lymphocytes as well as in brain tissue. Exposure of rat splenic lymphocytes in vitro to oxotremorine caused a time- and concentration-dependent decrease in the density of 3H-QNB binding sites. This decrease occurred only when incubation with oxotremorine was carried out at 37 degrees C and not at 0-4 degrees C, suggesting that it was not an artifact due to residual, unwashed, oxotremorine. The effect of oxotremorine was mimicked by two other cholinergic agonists, acetylcholine and carbachol, and was antagonized by atropine, which, when present alone, caused an increase in 3H-QNB binding. In vivo exposures to oxotremorine or atropine (both at 20 mg/kg/day for 14 days via an ALZA minipump) caused a significant decrease (20-30%) and increase (13-30%), respectively, of 3H-QNB binding in various brain areas as well as circulating lymphocytes. Repeated administrations of the organophosphorus insecticide disulfoton (2 mg/kg/day for 14 days, i.p.) caused significant reductions (59-88%) of acetylcholinesterase activity in brain, lymphocytes, plasma and red blood cells, as well as a 23-39% decrease of 3H-QNB binding in brain areas and circulating lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Costa
L G
LG
Department of Environmental Health, University of Washington, Seattle 98195.
Kaylor
G
G
Murphy
S D
SD
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D000110:Acetylcholinesterase